Gene survival in the Asian wild horse (Equus przewalskii): I. Dependence of gene survival in the calgary breeding group pedigree

The joint probability distribution of the number of distinct (not identical by descent) genes from each founder of the Equus przewalskii population that survive in the five horses of the Calgary Zoological Gardens breeding group has been calculated. The dependence structure of this distribution is investigated, and informative marginal distributions are given, among them the distributions of the genetic contributions of each founder to the Calgary horses and the distribution of wild-type genes in these horses. The dependence pattern is found to be complex; there is no substitute for exact calculation of the full joint probability distribution of numbers of surviving genes. Probabilities of gene survival give a more complete summary of the genetic structure of a set of individuals than is provided by more routine measures such as heterozygosity or founder contributions. The feasibility of computing these probabilities for small groups of current individuals descended from few founders via long and complex pedigrees, provides a new approach to assessing such groups, and could be used also in selecting animals to form the founder stock of propagules for future reintroduction programs.     

DNA sampling and banking in clinical genetics and genetic research

Health-related direct-to-consumer (DTC) genetic testing has been a controversial practice. Especially problematic is predictive testing for Alzheimer disease (AD), since the disease is incurable, prevention is inconclusive, and testing does not definitively predict an individual's future disease status. In this paper, I examine two contrasting cases of subjects who learn through genetic testing that they have an elevated risk of developing AD later in life. In these cases, the subject's emotional response to the result is related to how well prepared she was for the real-life personal implications of possible test results. Analysis leads to the conclusion that when groups of health-related genetic tests are offered as packages by DTC companies, informed consumer choice is rendered impossible. Moreover, I argue, this marketing approach contravenes US Federal Trade Commission policies for non-deceptive commercial communications. I conclude by suggesting ways to improve the prospects for informed consumer choice in DTC testing.     

Mate choice and the genetic basis for colour variation in a polymorphic dart frog: inferences from a wild pedigree

Understanding how reproductive barriers evolve during speciation remains an important question in evolution. Divergence in mating preferences may be a common first step in this process. The striking colour pattern diversity of strawberry dart frog (Dendrobates pumilio) populations has likely been shaped by sexual selection. Previous laboratory studies have shown that females attend to male coloration and prefer to court with males of their own colour, suggesting that divergent morphs may be reproductively isolated. To test this hypothesis, we used molecular data to estimate pedigree relationships from a polymorphic population. Whereas in the laboratory both red and yellow females preferred to court with males of their own phenotype, our pedigree shows a pattern of assortative mating only for red females. In the wild, yellow females appear to be less choosy about their mates, perhaps because they incur higher costs associated with searching than females of the more common red phenotype. We also used our pedigree to investigate the genetic basis for colour-pattern variation. The phenotype frequencies we observed were consistent with those expected if dorsal background coloration is controlled by a single locus, with complete dominance of red over yellow. Our results not only help clarify the role of sexual selection in reducing gene flow, but also shed light on the mechanisms underlying colour-pattern variation among sympatric colour morphs. The difference we observed between mating preferences measured under laboratory conditions and the pattern of mate choice observed in the wild highlight the importance of field studies for understanding behavioural reproductive isolation.     

Relationship type affects the reliability of dispersal distance estimated using pedigree inferences in partially sampled populations: A case study involving invasive American mink in Scotland

Estimating dispersal—a key parameter for population ecology and management—is notoriously difficult. The use of pedigree assignments, aided by likelihood‐based software, has become popular to estimate dispersal rate and distance. However, the partial sampling of populations may produce false assignments. Further, it is unknown how the accuracy of assignment is affected by the genealogical relationships of individuals and is reflected by software‐derived assignment probabilities. Inspired by a project managing invasive American mink (Neovison vison), we estimated individual dispersal distances using inferred pairwise relationships of culled individuals. Additionally, we simulated scenarios to investigate the accuracy of pairwise inferences. Estimates of dispersal distance varied greatly when derived from different inferred pairwise relationships, with mother–offspring relationship being the shortest (average = 21 km) and the most accurate. Pairs assigned as maternal half‐siblings were inaccurate, with 64%–97% falsely assigned, implying that estimates for these relationships in the wild population were unreliable. The false assignment rate was unrelated to the software‐derived assignment probabilities at high dispersal rates. Assignments were more accurate when the inferred parents were older and immigrants and when dispersal rates between subpopulations were low (1% and 2%). Using 30 instead of 15 loci increased pairwise reliability, but half‐sibling assignments were still inaccurate (>59% falsely assigned). The most reliable approach when using inferred pairwise relationships in polygamous species would be not to use half‐sibling relationship types. Our simulation approach provides guidance for the application of pedigree inferences under partial sampling and is applicable to other systems where pedigree assignments are used for ecological inference.     

Risk, medicine and women: a case study on prenatal genetic counselling in Brazil

Genetic counselling is an important aspect of prenatal care in many developed countries. This tendency has also begun to emerge in Brazil, although few medical centres offer this service. Genetic counselling provides prenatal risk control through a process of individual decision-making based on medical information, in a context where diagnostic and therapeutic possibilities overlap. Detection of severe foetal anomalies can lead to a decision involving possible termination of pregnancy. This paper focuses on medical and legal consequences of the detection of severe foetal anomalies, mainly anencephaly and Down syndrome, and in light of the fact that abortion is illegal in Brazil. The discussion is based on the literature and empirical research at a high-complexity public hospital in Rio de Janeiro.     

Estimating quantitative genetic parameters in wild populations: a comparison of pedigree and genomic approaches

The estimation of quantitative genetic parameters in wild populations is generally limited by the accuracy and completeness of the available pedigree information. Using relatedness at genomewide markers can potentially remove this limitation and lead to less biased and more precise estimates. We estimated heritability, maternal genetic effects and genetic correlations for body size traits in an unmanaged long‐term study population of Soay sheep on St Kilda using three increasingly complete and accurate estimates of relatedness: (i) Pedigree 1, using observation‐derived maternal links and microsatellite‐derived paternal links; (ii) Pedigree 2, using SNP‐derived assignment of both maternity and paternity; and (iii) whole‐genome relatedness at 37 037 autosomal SNPs. In initial analyses, heritability estimates were strikingly similar for all three methods, while standard errors were systematically lower in analyses based on Pedigree 2 and genomic relatedness. Genetic correlations were generally strong, differed little between the three estimates of relatedness and the standard errors declined only very slightly with improved relatedness information. When partitioning maternal effects into separate genetic and environmental components, maternal genetic effects found in juvenile traits increased substantially across the three relatedness estimates. Heritability declined compared to parallel models where only a maternal environment effect was fitted, suggesting that maternal genetic effects are confounded with direct genetic effects and that more accurate estimates of relatedness were better able to separate maternal genetic effects from direct genetic effects. We found that the heritability captured by SNP markers asymptoted at about half the SNPs available, suggesting that denser marker panels are not necessarily required for precise and unbiased heritability estimates. Finally, we present guidelines for the use of genomic relatedness in future quantitative genetics studies in natural populations.     

On the neutrality of molecular genetic markers: pedigree analysis of genetic variation in fragmented populations

Many studies employ molecular markers to infer ecological and evolutionary processes, assuming that variation found at genetic loci offers a reliable representation of stochastic events in natural populations. Increasingly, evidence emerges that molecular markers might not always be selectively neutral. However, only a few studies have analysed how deviations from neutrality could affect estimates of genetic variation, using populations with known genealogy. We monitored changes in allozyme variation over eight generations in captive metapopulations of the butterfly Bicyclus anynana. Population demography was recorded by individually marking 35 000 butterflies and constructing pedigrees. We designed a computer program that simulated the inheritance of founder allozyme alleles in butterfly pedigrees. We thus tested whether the observed transmission of allozyme alleles could be explained by random genetic drift alone, or whether there was evidence for positive or negative selection. This analysis showed that in the smallest metapopulations the loss of allozyme variation exceeded the neutral rate. Possibly, linkage disequilibria between deleterious mutations and marker alleles resulted in background selection and a faster erosion of allozyme variation. In larger metapopulations, one locus (MDH) showed a significant heterozygote excess and smaller than expected loss in heterozygosity, observations consistent with (associative) overdominance. This study demonstrates that the neutrality of molecular markers cannot always be assumed, particularly in small populations with a high mutation load.     

Prevalence of genetic variants associated with cardiovascular disease risk and drug response in the Southern Indian population of Kerala

BACKGROUND AND AIM:

This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala.

MATERIALS AND METHODS:

Genomic DNA isolated from 100 out-patient samples from Kerala were sequenced to examine the frequency of clinically relevant polymorphisms in the genes MYBPC3 (cardiomyopathy), SLCO1B1 (statin-induced myopathy), CYP2C9, VKORC1 (response to warfarin) and CYP2C19 (response to clopidogrel).

RESULTS:

Our analyses revealed the frequency of a 25 bp deletion variant of MYBPC3 associated with risk of cardiomyopathy was 7%, and the SLCO1B1 “C” allele associated with risk for statin-induced myopathy was 15% in this sample group. Among the other variants associated with dose-induced toxicity of warfarin, VKORC1 (c.1639G>A), was detected at 22%, while CYP2C9*3 and CYP2C9*2 alleles were present at a frequency of 15% and 3% respectively. Significantly, the tested sample population showed high prevalence (66%) of CYP2C19*2 variant, which determines response to clopidogrel therapy.

CONCLUSIONS:

We have identified that certain variants associated with cardiovascular disease and related drug response in the five genes, especially those in VKORC1, CYP2C19 and MYBPC3, are highly prevalent in the Kerala population, with almost 2 times higher prevalence of CYP2C19*2 variant compared with other regions in the country. Since the variants chosen in this study have relevance in disease phenotype and/or drug response, and are detected at a higher frequency, this study is likely to encourage clinicians to perform genetic testing before prescribing therapy.     

Pedigree analysis of the Turkish Arab horse population: structure,inbreeding and genetic variability

The aim of this study was to evaluate genetic variability in the Turkish Arab horse population using pedigree information. This study is the first detailed pedigree analysis of the breed in Turkey. Pedigree data were collected from the National Studbook. The pedigree data for 23 668 horses, born between 1904 and 2014, were used in the analysis. From this data set, a reference population (RP) of 14 838 animals symbolising the last generation was defined. Demographic parameters, the inbreeding level (F), the average relatedness (AR), the effective population size (N_e), the effective number of founders (f_e), the effective number of ancestors (f_a) and the number of founder genome equivalents (f_g) were calculated for the population. The average generation interval for the RP was 12.2±4.6 years, whereas the calculated pedigree completeness levels were 98.2%, 96.6% and 95.0% for the first, second and third known generations. The mean equivalent generations (t), the average complete generations and the mean maximum generations for the RP were 7.8, 5.4 and 12.2, respectively, whereas the meanFand AR were 4.6% and 9.5% for the RP. The rate of inbred animals was 94.2% for the RP, whereas the number of founders, the number of ancestors and thef_e,f_aandf_gwere 342, 223, 40, 22 and 9.6 for the RP. The large differences observed betweenf_e, and the number of founders demonstrates that genetic diversity decreased between the founder and the RP. Contribution of the 14 most influential founder to the RP was 50.0%, whereas just eight ancestral horses can account for 50% of the genetic variability.N_eestimated via an individual increase in inbreeding per generation (${\overline{N}}_{\text{e}}$), and paired increase in coancestry$\left(\text{}{\overline{N}}_{eC}\right)$, were 74.4±3.9 and 73.5±0.58, respectively. The inbreeding increases with the pedigree knowledge. In addition, the decrease in inbreeding in last years is more noticeable.     

中国出生缺陷遗传学研究的回顾与展望

减少出生缺陷是我国“健康中国2030”规划中的重要组成部分。遗传因素单独或协同作用导致了超过80%的出生缺陷疾病。与出生缺陷相关的遗传学研究可为临床筛查、诊断和治疗提供精准的分子靶标。我国的出生缺陷遗传学研究自20世纪60年代以来取得了长足的发展。同时,随着相关研究成果的不断涌现,以遗传咨询和检测为核心的临床转化工作也在不断深化和完善。基础研究与临床应用的紧密结合,将为我国孕育“健康孩”提供可靠的技术保障。本文首先回顾了我国出生缺陷遗传学研究的历史,继而介绍当前国内外出生缺陷遗传学研究的现状和热点,最后对未来的研究方向及相关的临床应用趋势进行展望和讨论,旨在为读者提供了一个全局性的视角来认知我国的出生缺陷遗传学研究发展之路。     

Estimating genetic correlations in natural populations in the absence of pedigree information: accuracy and precision of the Lynch method

Usually, genetic correlations are estimated from breeding designs in the laboratory or greenhouse. However, estimates of the genetic correlation for natural populations are lacking, mostly because pedigrees of wild individuals are rarely known. Recently Lynch (1999) proposed a formula to estimate the genetic correlation in the absence of data on pedigree. This method has been shown to be particularly accurate provided a large sample size and a minimum (20%) proportion of relatives. Lynch (1999) proposed the use of the bootstrap to estimate standard errors associated with genetic correlations, but did not test the reliability of such a method. We tested the bootstrap and showed the jackknife can provide valid estimates of the genetic correlation calculated with the Lynch formula. The occurrence of undefined estimates, combined with the high number of replicates involved in the bootstrap, means there is a high probability of obtaining a biased upward, incomplete bootstrap, even when there is a high fraction of related pairs in a sample. It is easier to obtain complete jackknife estimates for which all the pseudovalues have been defined. We therefore recommend the use of the jackknife to estimate the genetic correlation with the Lynch formula. Provided data can be collected for more than two individuals at each location, we propose a group sampling method that produces low standard errors associated with the jackknife, even when there is a low fraction of relatives in a sample.     

Association of the genetic polymorphisms in immunoinflammatory microRNAs with risk of ischemic stroke and subtypes in an Iranian population

Stroke is one of the most common type of cerebrovascular disease threatening human health and life with high mortality, disability, and morbidity. Ischemic stroke (IS) is determined to be a complex disease containing a group of heterogeneous disorders with various environmental and genetic risk factors. This study evaluated the polymorphisms of microRNAs involved in inflammatory routes leading to stroke in an Iranian population. This study evaluated the associations of hsa-mir-608 C/G rs4919510, hsa-mir-499 A/G rs3746444, and hsa-mir-145 C/T rs190323149 polymorphisms in precursor miRNAs with the risk of IS. These microRNA polymorphisms were analyzed in 470 patients with IS and 489 control subjects. The TOAST criteria was applied for IS subtypes classification. The frequency of the allele G of hsa-mir-499/rs3746444 A/G revealed significant association with IS in comparison with controls ( p < 0.0001, OR = 1.838, 95% CI = 1.406–2.401). Increased IS risks were associated with hsa-mir-499/ rs3746444 A/G genotypes in diverse genetic model (homozygote comparison: p = 0.004, OR = 2.136, 95% CI = 1.269–3.597; heterozygote comparison: p = 0.029, OR = 1.373, 95% CI = 1.033–1.825). Statistical analysis in IS subtypes showed that cardio-embolic patients compared with other subtypes (large artery atherosclerosis and lacunar) had higher frequency of G allele (LAA vs. CEI, p = 0.017; LAC vs. CEI, p = 0.009), AG genotype (LAA vs. CEI, p = 0.016; LAC vs. CEI, p = 0.013). Nevertheless, this study did not find any association between the alleles and genotypes of mir-608 C/G rs4919510 SNP and IS, respectively ( p > 0.05). The current investigation provided verification that hsa-mir-499 rs3746444 A/G polymorphism may be associated with a significantly increased risk of IS in an Iranian population.     

Lay perceptions of genetic testing in Germany and Israel: the interplay of national culture and individual experience

Germany and Israel represent opposite regulatory approaches and bioethical outlooks regarding genetic testing. This study examines lay attitudes (including attitudes of people affected by genetic diseases) in both countries towards genetic testing of adults, focusing on the differences between cultural and personal argumentations, as well as between affected and non-affected perspectives. With regard to three major emerging themes – medical technology/technocratic medicine; economic aspects of healthcare; and personal decision-making – a national contrast was apparent on the cultural level of argumentation, but not in the personal context of decision-making or in the concerns of people affected by genetic diseases. We conclude by discussing the interplay of national culture and individual experience in constructing arguments about the harms and benefits of genetic testing, and the implications for the study of cross-cultural bioethics in the context of “genetic responsibility”.     

Gene survival in the Asian wild horse (Equus przewalskii): II. Gene survival in the whole population,in subgroups,and through history

In populations with a known pedigree, exact joint probability distributions of numbers of surviving of genes from each founder can now be calculated for moderately large complex pedigrees (1,000–2,000 individuals and much inbreeding). The usefulness of such calculations is shown by our analysis of gene survival in the Asian wild horse (Equus przewalskii), a species now extinet in the wild with a captive population with 1,516 individuals in the known pedigree (12 generations). We calculate the genetic diversity of subsets of the current population interesting to the North American Species Survival Plan, trace the loss of genetic diversity in this species through its history in captivity, and determine genetically important individuals in the North American population—those with relatively high probabilities of having unique copy genes (genes not found in any other living individual in North America).     

DNA amplification fingerprinting as a tool for checking genetic purity of strains in the cyanobacterial inoculum

Summary The electrophoretic patterns for 17 different cyanobacterial cultures derived from 6 different decamer primers were analysed to provide diagnostic fingerprints for each culture and their genetic distances based on RAPD markers.The primer OPB 09 produced a maximum of 24 amplified products. The primers OPB 09, OPG 04 and OPAH 02 generated markers specific for Nostoc cultures. Westiellopsis was found to be distinct from other cyanobacterial cultures in the RAPD profile obtained with the primer OPAH 02. The primer OPF 03 generated specific markers for Tolypothrix tenuis. Fischerella cultures could be identified with the primers OPB 09, OPAG 03 and OPF 05. The study revealed that these RAPD markers could be further used to identify and establish the genetic purity of the strains in the cyanobacterial inoculum. There was a similarity of 60–90% within Westiellopsis cultures. Nostoc cultures shared 50–80% similarity with Westiellopsis cultures. Anabaenacultures were similar to Westiellopsiscultures by 60–70. The markers produced for each culture were also applied to phylogenetic analysis to infer genetic relatedness in this group of prokaryotes. The dendrogram analysis clearly revealed that free-living cyanobacterial cultures are closely related to each other and are distinct from the symbiotic forms.     

Adaptation of the AFLP technique as a new tool to detect genetic instability and transposition in interspecific hybrids

An adapted amplified fragment length polymorphism (AFLP) protocol is presented for detection of hybrid instability in the genome of interspecific hybrids between Drosophila buzzatii and D. koepferae species. Analyses of 15 AFLP instability markers (new bands detected in hybrids) show that up to 81% are the result of transposable element (TE) activity. Twenty TEs associated with AFLP instability markers have been detected by this method in backcross hybrids and segmental hybrids, demonstrating its validity in detecting transposition events occurring during the hybridization process. New insertions of Helena TE have been observed in the hybrid genome after hybridization of the TGTCG22 instability marker by FISH. The AFLP marker technique proved to be an efficient method that improves upon traditional and bioinformatic tools previously used to detect TE mobilization. This newly adapted AFLP protocol may also be applied to a large number of organisms outside the Drosophila genus, making it of interest to evolutionary and population genetic researchers working with species where the knowledge of the genome is scarce.     

Symbolic ethnicity and Herbert Gans: race,religion, and politics in the twenty-first century

This article attempts to assess some of Herb Gans’s influential contributions, not only in his important paper on symbolic ethnicity, but also his wider discussion of the changing role of race, ethnicity, and religion in American society. In a period spanning more than half a century, he has helped to raise key questions and to suggest avenues of research that have stimulated debates and the re-evaluation of a complex, controversial, and highly dynamic field of social science research and policy.     

Body mass index and depressive symptoms: instrumental‐variables regression with genetic risk score

The causal role of obesity in the development of depression remains uncertain. We applied instrumental‐variables regression (Mendelian randomization) to examine the association of adolescent and adult body mass index (BMI) with adult depressive symptoms. Participants were from the Young Finns prospective cohort study (n = 1731 persons, 2844 person‐observations), with repeated measurements of BMI and depressive symptoms (modified Beck's Depression Inventory). Genetic risk score of 31 single nucleotide polymorphisms previously identified as robust genetic markers of body weight was used as a proxy for variation in BMI. In standard linear regression analysis, higher adult depressive symptoms were predicted by higher adolescent BMI (B = 0.33, CI = 0.06–0.60, P = 0.017) and adult BMI (B = 0.47, CI = 0.32–0.63, P < 0.001). These associations were replicated in instrumental‐variables analysis with genetic risk score as instrument (B = 1.96, CI = 0.03–3.90, P = 0.047 for adolescent BMI; B = 1.08, CI = 0.11–2.04, P = 0.030 for adult BMI). The association for adolescent BMI was significantly stronger in the instrumented analysis compared to standard regression (P = 0.04). These findings provide additional evidence to support a causal role for high BMI in increasing symptoms of depression. However, the present analysis also demonstrates potential limitations of applying Mendelian randomization when using complex phenotypes.